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Name:	Nael A. McCarty
Position:	Associate Professor of Pediatrics Associate Professor of School of Biology, GA Tech
Degree:	Ph.D., University of Texas Health Sciences Center, 1990 M.S., University of North Carolina, 1987
Programs:	MSP, Full Member
Phone:	404 727-1327
Address:	2015 Uppergate Dr, NE, 2172-001-1AA
Email:	nael.mccarty@biology.gatech.edu
Website:	http://www.biology.gatech.edu/faculty/nael-mccarty/
Research Descriptions:
Short:	Structure and function of the ATP-binding cassette (ABC) transporters; pathophysiology in cystic fibrosis.
Long:	Cystic Fibrosis (CF) is a complex lethal disorder, which affects approximately 1:2500 Caucasians in this country and is manifest in multiple tissues of epithelial origin. Mutations in the gene encoding the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) result in abnormal secretion in exocrine glands, due to dysfunctional ion channels and/or improper regulation of ion channels in response to stimulation of the protein kinase A (PKA) signal transduction pathway. This laboratory is actively engaged in research addressing three aspects of Cystic Fibrosis: 1) The biophysics and regulation of the CFTR chloride channel. CFTR forms a low-conductance Cl channel which is controlled in a novel way. A major effort in this lab involves performing structure/function experiments to determine which portions of the protein are important in the process of permeation (how ions move "through" the protein between the extracellular and intracellular fluids) and in the process of gating (how the channel is turned "on" and "off" by the regulatory domains of the protein). 2) Control of the apical membrane transport complex. Part of the complexity of this disease stems from the multifunctional role of the CFTR protein. CFTR regulates the epithelial sodium channel (ENaC) and a separate Cl channel in airway apical membranes. Hence, CFTR may be the molecular switch that balances absorptive and secretory processes in these cells, and thus may serve as the "master regulator" in the apical membrane transport complex. However, the mechanistic details of these interactions are unknown. Our data suggest that the CFTR and ENaC proteins interact directly, perhaps via their cytoplasmic domains. We are determining what the hallmarks of this interaction are, and asking how mutations in the CFTR gene disrupt the interaction. 3) Physiological basis of genetic disease. Over 850 disease-causing mutations have been identified in the CFTR gene. However, not all of these mutations lead to severe lung disease. The relationship between genotype and phenotype is not yet well understood. Emory's campus houses a CF treatment center, which provides care for 500 CF patients. Through our extensive collaboration with the treatment center and Egleston and Emory hospitals, we are attempting to take genotype/phenotype studies to a new physiological level. For this work, we study the function of the Cl- and Na+ channels in vivo in CF patients, and in vitro in airway cells removed in surgical procedures. This work also allows us to be involved in the development of novel therapies for CF. We are currently collaborating in two clinical trials for novel gene-assist therapies, and will soon join a clinical trial for liposome-mediated gene therapy for CF. This multifaceted approach keeps our efforts focused upon issues relevant to this disease and its treatment.